Toward Outcome Measurement of Anxiety in Youth with Autism Spectrum Disorders

描述(由申请人提供)：这个为期四年的多站点项目将在未来的自闭症谱系障碍(ASDS)青少年临床试验中推进焦虑的结果测量。项目公告(PAR-11-045)声称，发育障碍人群中缺乏结果衡量标准是发育障碍人群药物研究的主要障碍。焦虑障碍在患有自闭症和看似合理的治疗目标的年轻人中很常见，但研究很少(White等人，2009；van Steensel等人，2011；King 等人，2009年)。在典型的发展中青年中，有被广泛接受的焦虑结果衡量标准(Rupp焦虑组，2001年；Walkup等人，2008年)。鉴于自闭症患者的语言和认知缺陷，如果不进行修改，这些措施不适合患有自闭症的青少年。患有自闭症的青少年焦虑的结果衡量标准的必要性也被消费者团体注意到(WWW。AutismSpeaks.org)。我们聚集了一支优秀的研究人员和顾问团队，开发了一种父母评级和临床医生评级的工具，用于测量参与临床试验的患有自闭症的青年患者的焦虑程度。我们提出了一种与FDA专著一致的混合方法：患者报告的结果测量：在医疗产品开发中使用以支持标签声明(www.fda.gov/CDER/Guidance)。在一年级，与父母一起的焦点小组将探索患有自闭症儿童的焦虑表现。这些信息将被用来改进CASI焦虑量表(基于DSM-IV的父母评级)和修改临床医生评级的儿科焦虑量表(PARS)。YR 2将在一个安全的网站上收集900名5至17岁ASD儿童的修订CASI ANX量表(20-25个条目)的数据。我们将检验该父母评定量表的分布、内部一致性、因素结构和项目分析。该量表的重测信度将在在线样本中进行评估 受访者和亲自评估的受试者样本。CASI ANX量表的有效性将通过与另一种父母评定的焦虑指标(趋同效度)以及与重复行为、社交障碍和易怒指标(发散效度)的相关性进行对比来评估。修订的PAR将通过对90名受试者的面对面评估来收集，以评估第3年的可靠性(评价者之间的内部一致性)和有效性。在第34年，高焦虑亚组(CASI ANX量表上的阈值以上)将在心率[HR]、心率变异性[HRV]和皮肤电活动[EDA]的生理指标上与对照组(ASD伴低焦虑)进行比较。HR、HRV和EDA将在休息和轻度焦虑的情况下进行测量。这项探索性研究的结果可能会为自闭症患者早期测试化合物的焦虑症确定读数。该项目有四个交付成果：焦点小组结果(第2年)；可靠和有效的父母评估的焦虑结果衡量标准(第3年)；可靠和有效的临床医生评估的焦虑衡量标准(第4年)；初步的HRV和EDA结果(在资助期结束后不久)。 与公共卫生相关：自闭症谱系障碍(ASD)是一种致残疾病，估计每1000名儿童中就有9名儿童(大约45万名5至17岁的美国儿童)。至少三分之一(15万)患有自闭症的青年因焦虑问题而进一步残疾。该项目的重点是对患有自闭症的青少年的焦虑结果进行衡量，这是推进药物和心理社会治疗的先决条件。

DESCRIPTION (provided by applicant): This four-year multisite project will advance outcome measurement of anxiety in future clinical trials in youth with autism spectrum disorders (ASDs). Program announcement (PAR-11-045) declares that the dearth of outcome measures in developmentally disabled populations is a major impediment for drug research in developmentally disabled populations. Impairing anxiety is common in youth with ASDs and a plausible treatment target, but poorly studied (White et al., 2009; van Steensel et al., 2011; King et al., 2009). There are well-accepted outcome measures for anxiety in typically developing youth (RUPP Anxiety Group, 2001; Walkup et al., 2008). Given the language and cognitive deficits in ASDs, these measures are not suitable for youth with ASDs without modification. The need for outcome measures for anxiety in youth with ASDs has also been noted by consumer groups (www. autismspeaks.org). We have assembled an outstanding team of investigators and consultants to develop a parent-rated and a clinician-rated instrument for measuring anxiety in youth with ASDs who participate in clinical trials. We propose a mixed method approach in line with the FDA monograph: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (www.Fda.Gov/Cder /Guidance). In Yr 1, focus groups with parents will explore the manifestations of anxiety in children with ASDs. This information will be used to refine the CASI Anxiety scale (DSM-IV-based parent-rating) and modify the clinician-rated Pediatric Anxiety Rating Scale (PARS). Yr 2 will collect data on the revised CASI Anx scale (20-25 items) in 900 children with ASD ages 5 to 17 years on a secure web site. We will examine the distribution, internal consistency, factor structure and item analysis of this parent-rated scale. Test-retest reliability of the scale will be evaluated in a subsample of online respondents and a sample of subjects assessed in person. Validity of the CASI Anx scale will be evaluated by contrasting the correlations with another parent-rated measure of anxiety (convergent validity) and with measures of repetitive behavior, social disability and irritability (divergent validity). The revised PARS will be collected via in person assessments of 90 subjects to evaluate reliability (inter-rater, internal consistency) and validity in Yr 3. In Yrs 34, a high anxiety subgroup (above threshold on the CASI Anx scale) will be compared to controls (ASD with low anxiety) on physiological measures of heart rate [HR], heart rate variability [HRV] and electrodermal activity [EDA]). HR, HRV and EDA will be measured at rest and under mildly anxiety provoking conditions. Results from this exploratory investigation may identify read outs for early testing of compounds for anxiety in ASDs. The project has four deliverables: focus group results (Yr 2); a reliable and valid parent-rated anxiety outcome measure (Yr 3); a reliable and valid clinician-rated anxiety measure (Yr 4); preliminary HRV and EDA findings (soon after the grant period). PUBLIC HEALTH RELEVANCE: Autism Spectrum Disorders (ASDs) are disabling conditions affecting an estimated 9 per 1000 children (roughly 450,000 American children between age 5 and 17 years). At least a third (150,000) of youth with ASDs is further disabled by anxiety problems. This project is focused on outcome measurement of anxiety in youth with ASDs, which is a prerequisite for advancing drug and psychosocial treatments.